In its wake, the pandemic left a legacy: Descendants of the virus have caused almost all influenza A pandemics since 1918, though all were relatively mild compared with the first. According to Jeffery K. Taubenberger, MD, PhD, the first scientist to sequence the 1918 genome, the H1N1 virus associated with today’s pandemic is a fourth-generation descendant of the 1918 virus.
The pandemic also left mysteries.
From spring 1918 to spring 1919, three waves of influenza swept through Europe, Asia and North America. The first wave, in the United States concentrated in military camps and urban areas, began in March, with the virus infecting a large number of people but not causing an extraordinary number of deaths. The deadly second wave struck simultaneously in the Northern and Southern hemispheres from September to November, and the third wave hit pockets in spring 1919.
Though many experts attribute all three waves to the same H1N1 virus, Taubenberger, chair of the Department of Molecular Pathology at the Armed Forces Institute of Pathology in Rockville, Md., has expressed doubts, saying the difference in death rates would represent a mutation. Evidence indicates profound viral mutations take years to develop and then months to spread around the world; the gap between the first and second wave involved just months, and the second wave struck in many areas of the world at the same time. Because researchers have recovered tissue samples from only the second wave, no conclusive evidence about the first and third exists.
According to Taubenberger, sequence data also suggest that the entire 1918 virus was novel to humans at the time. But what was the source? Taubenberger calls the flu “avian-like” but notes researchers have uncovered no avian influenza genes that provide a good match for the 1918 virus. At the same time, Taubenberger says, the 1918 sequences have too few amino acid differences from those of wild-bird strains to have spent many years adapting in a human or swine host.
The severity of the pandemic begs another question: Could it happen again? Modern medical interventions and preventions make the scenario seem unlikely. No antibiotics to fight the pneumonia that often accompanies influenza existed in 1918, and Taubenberger believes the virus would be vulnerable to the anti-flu drugs available today. Vaccinations—possible only in pandemics that begin with an early wave, as did the pandemic today—also were unavailable. Physicians had no tools to help hospitalized patients overcome breathing distress.
Taubenberger says the unanswered questions from 1918 make a definitive conclusion impossible. But, he says, “We can only conclude that since it happened once, analogous conditions could lead to an equally devastating pandemic.”